View clinical trials related to Aphasia, Primary Progressive.
Filter by:The purpose of this study is to determine the safety and engraftment of donor hematopoietic cells using this conditioning regimen in patients undergoing a hematopoietic (blood forming) cell transplant for an inherited metabolic storage disease.
Amyotrophic lateral sclerosis (ALS) with frontotemporal dementia (FTD) is a rare clinical entity, in which both disorders are variably associated in the same patient or within the family. This adult-onset disorder, which is rapidly fatal, occurs in some families with autosomal dominant (AD) transmission and age-dependant penetrance. Two studies have provided evidence for linkage of this condition to chromosomes 15 (in a single family) and 9 (in five families). However, none of these loci have been yet confirmed. Through a national network of 10 centres with specialists for FTD and/or ALS, we have identified 35 probands with ALS-FTD, including 13 with a family history consistent with AD inheritance. Mutations in the SOD1 and tau genes, respectively responsible for autosomal dominant forms of ALS and FTD, will be excluded by direct sequencing. We will then extend the pedigree of the 13 autosomal dominant families to all consenting first, second and eventually third degree relatives, using well defined criteria for FTD and ALS. The same strategy will be applied to newly identified families during the course of the project (at least, seven families with AD inheritance expected). Linkage studies will be performed in the 20 families using markers from the two candidate regions on chromosomes 9 and 15. Then, refinement of the candidate region will be obtained by analyzing the linked families with a high density of microsatellite markers. This should lead to the refinement of the candidate regions, allowing to search for mutations in candidate genes. Genes located within the critical regions will be prioritized for their analysis by sequencing, according to their expression in the nervous system and to their function. Once the responsible gene(s) will be identified, it will then possible to define its spectrum of mutations and to establish genotype/phenotype correlations. Alternatively, if none of the candidate regions is confirmed, a genome wide search will be performed, allowing to identify one or more loci for ALS-FTD. The same strategy would then be applied to identify the corresponding gene(s). This project should contribute for identifying the molecular basis of this devastating disorder with practical consequences for genetic counselling in ALS-FTD families, and with the perspective of elucidating the pathophysiology of this disorder.
The purpose of this clinical trial is to test whether or not the medication amantadine is effective in reducing behavioral disturbances in patients with frontotemporal dementia.
Objectives. The proposed clinical study has two goals: First, to assess the efficacy of a central nervous system stimulant and an atypical antipsychotic in treating the behavioral symptoms of FTD and second, to further characterize the biological markers, including genetic, imaging, and CSF proteins, of FTD in relation to our existing group of Alzheimer's patients. Rationale. Frontotemporal dementia (FTD) is increasingly recognized as an important neuropsychiatric disorder. Symptoms of FTD include disinhibition, impulsivity, apathy, affective lability, and language dysfunction. The clinical syndrome is associated with frontal and/or anterior temporal atrophy on imaging and autopsy. Levels of the CSF proteins tau and (Beta)-amyloid 1-42, shown to have diagnostic utility in patients with Alzheimer's Disease (AD), have also been found to be abnormal in FTD. FTD is less associated with APOE genotype than AD, however some familial cases of FTD are associated with specific mutations in the gene encoding the tau protein. Currently, no treatments have been proven to be effective for altering the course or clinical symptoms of FTD. Design. Study subjects will include 50 male and female patients with mild-moderate frontotemporal dementia recruited from participants in NINDS protocol 02-N-0001. In a double-blinded crossover 11-week study without a placebo control, patients will be treated with a stimulant (dextroamphetamine) and an atypical antipsychotic (quetiapine). The primary outcome measures will be the Neuropsychiatric Inventory and the Clinical Global Impression of Change. Cerebrospinal fluid, cognitive and genetic measures, brain MRIs, and side effects scales will also be collected.
This pilot study will evaluate the effect of direct current (DC) electrical polarization of the brain on language, memory, reaction time, and mood in six patients with frontotemporal dementia (Pick's disease). There is no effective treatment available for cognitive impairment in patients with this condition. DC polarization sends a very weak current between two sponge pads placed on the head. In a previous study in healthy volunteers, DC polarization of the left prefrontal area of the brain increased verbal fluency, memory and attention, and motor reaction time in the study subjects. Patients between 35 and 75 years of age with frontotemporal dementia who have been referred to NINDS's Cognitive Neuroscience Section for an existing protocol will be offered participation in this study. Candidates will be screened with a neurological examination to confirm the diagnosis of frontotemporal dementia. Participants receive 40 minutes of DC polarization or sham polarization in each of two separate sessions. (No current is applied in the sham treatment). During the polarization, the patient rests quietly. Sponge pads that have been soaked in water are put on the left side of the head and above the right eye, and are held in place with elastic netting. Before the polarization and after about 20 minutes of polarization, patients undergo the following tests: - Language: Patients must say as many words beginning with certain letters as they can in 90 seconds. - Memory: Patients must remember a letter on a computer screen, and when the letter appears again, press the same letter on the keyboard. - Reaction time: Patients place pegs on a pegboard. - Mood: Patients place a mark on a line ranking how they feel.
OBJECTIVES: I. Evaluate bronchoalveolar lavage fluid and serum obtained from pediatric patients with storage disorders prior to allogeneic hematopoietic stem cell transplantation (HSCT) for the presence of proinflammatory cytokines and for the production of nitric oxide by alveolar macrophages to identify possible risk factors for pulmonary complications. II. Investigate the underlying mechanism for the development of significant pulmonary complications in these patients during HSCT. III. Evaluate bronchoalveolar lavage fluid and serum obtained from these same patients at the time a pulmonary complication develops post-HSCT, or at 60 days post-HSCT if there has been no pulmonary complications.
The main source of energy for the brain comes from a combination of oxygen and glucose (sugar). For brain cells to function normally they must receive a constant supply of these nutrients. As areas of the brain become more active blood flow into and out of these areas increase. In addition to oxygen and glucose, the brain uses chemical compounds known as phospholipids. These phospholipids make up the covering of nerve cells that assist in the transfer of information from cell to cell. Without phospholipids brain cell activity may become abnormal and cause problems in the nervous system. Certain diseases like Alzheimer's disease and brain tumors can affect blood flow to the brain and change the way the brain metabolizes phospholipids. In addition to diseases, changes in the brain occur with normal healthy aging. This study is designed to use PET scan to measure changes in blood flow and changes in phospholipid metabolism. Using this technique, researchers can improve their understanding of how certain diseases change the shape and function of the brain.